• Source: Vorasidenib

Vorasidenib, sold under the brand name Voranigo, is an anti-cancer medication used for the treatment of certain forms of glioma. Vorasidenib is a dual mutant isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 (mIDH1/2) inhibitor.
The most common adverse reactions include fatigue, headache, increased risk of COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures.
Vorasidenib was approved for medical use in the United States in August 2024. It is the first approval by the US Food and Drug Administration (FDA) of a systemic therapy for people with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation.




Medical uses


Vorasidenib is indicated for the treatment of people aged twelve years of age and older with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation, following surgery including biopsy, sub-total resection, or gross total resection.




Side effects


The most common adverse reactions include fatigue, headache, increased risk of COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizures. The most common grade 3 or 4 laboratory abnormalities include increased alanine aminotransferase, increased aspartate aminotransferase, GGT increased, and decreased neutrophils.




Pharmacology


Agios Pharmaceuticals previously developed the mIDH1 inhibitor ivosidenib and mIDH2 inhibitor enasidenib for treatment of acute myeloid leukemia (AML) with susceptible IDH1 or IDH2 mutations, respectively. However, ivosidenib and enasidenib have low brain exposure, precluding their use in gliomas. Moreover, isoform switching between IDH1 and IDH2 has been observed as a mechanism of resistance to mIDH inhibitor therapy. Vorasidenib was thus developed to improve blood-brain barrier penetration and inhibit both mIDH1/2.




History


Efficacy was evaluated in 331 participants with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation following surgery enrolled in INDIGO (NCT04164901), a randomized, multicenter, double-blind, placebo-controlled trial. Participants were randomized 1:1 to receive vorasidenib 40 mg orally once daily or placebo orally once daily until disease progression or unacceptable toxicity. Isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test. Participants randomized to placebo were allowed to cross over to vorasidenib after documented radiographic disease progression. Participants who received prior anti-cancer treatment, including chemotherapy or radiation therapy, were excluded.




Society and culture






= Legal status

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Vorasidenib was approved for medical use in the United States in August 2024.
The FDA granted the application for vorasidenib priority review, fast track, breakthrough therapy, and orphan drug designations.




References






Further reading






External links


Clinical trial number NCT04164901 for "Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)" at ClinicalTrials.gov
Clinical trial number NCT02481154 for "Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation" at ClinicalTrials.gov
Clinical trial number NCT03343197 for "Study of AG-120 and AG-881 in Subjects With Low Grade Glioma" at ClinicalTrials.gov

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